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HI scientists publish research advancing understanding of bile duct cancer

Scientists at The Hormel Institute published new research surrounding cholangiocarcinoma, a bile duct cancer and deadly form of liver cancer with no effective pharmacologic therapy available.

The article “Histone Deacetylase SIRT1 promotes loss of primary cilia in Cholangiocarcinoma” was published in Hepatology (2021). The research was a collaborative effort between The Hormel Institute, the Masonic Cancer Center, Mayo Clinic, and several institutions in Italy. The authors include Dr. Sergio Gradilone, Associate Professor and head of the Cancer Cell Biology and Translational Research lab at The Hormel Institute, and Dr. Kishor Pant, who works in Dr. Grandilone’s lab. Pant served as first author on this paper.

“This research is significant because it will contribute to a new understanding of HDACs and their effect on cilia formation and provide possible new targets for cholangiocarcinoma prevention and control,” Pant said.

Cilia are hair-like structures protruding from the cellular membrane. The primary cilium is like an antenna that almost every cell in our bodies have. Research shows that tumor cells eliminate this cellular antenna which gives them the chance to grow and move faster. Therefore, it’s important to understand the mechanisms that cancer cells use to get rid of primary cilia in order to inhibit this process and reduce the growth and migration ability of tumor cells. Pant and his team of collaborators found one of the mechanisms that bile duct cancer cells use to eliminate cilia.

“SIRT1 is a protein deacetylase known to act as a tumor promoter or suppressor in different cancers,” Gradilone said. “We found a novel mechanism of SIRT1-induced destabilization of primary cilia in cholangiocarcinoma.”

This discovery could lead to developing new treatments for cholangiocarcinoma.

“Cholangiocarcinoma usually develops without pain, therefore, its identification is generally made at a late stage when surgical treatments are excluded, leaving patients with insufficient therapeutic choices,” Gradilone said. “Therefore the development of novel therapeutic approaches is key.”

The full article can be found at https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.32080.